The ETS2 promoter contains an extended region of purine/pyrimidine strand asymmetry (CT tract) upstream from the start of transcription. The presence of these sequences is required for full ETS2 expression. The ETS2 CT tract was found to bind to a number of sequence-specific factors, one of which was identified as the transcription factor Sp1. Sp1 was shown to induce expression from the ETS2 promoter and the loss of putative Sp1 sites correlated with a loss of promoter activity in vivo. The transcriptional activator Pur-alpha was found to bind single-stranded DNA with a sequence specificity corresponding to the purine-rich strand of the ETS2 CT tract. These results suggest that ETS2 expression may be linked to cell cycle events through the interaction of Sp1 bound to the ETS2 promoter with a complex containing Pur-alpha.